The long-range goal of this research is to understand the cellular and molecular mechanisms that mediate the normal performance and adaptive plasticity of the vestibulo-ocular reflex (VOR). The VOR prevents blurred vision during self-motion by producing eye movements that precisely compensate for motion of the head. Neuronal mechanisms of plasticity enable the VOR to perform accurately in the face of development, trauma, and disease. Although the roles of particular classes of neurons to signal transformations and plasticity have been identified, little is understood about how cellular mechanisms contribute to the day-to-day performance and adaptive capabilities of the VOR. The objective of the proposed research is to elucidate how cerebellar activity influences signalling and plasticity in distinct classes of vestibular nucleus neurons. The central hypothesis is that central vestibular and cerebellar synapses onto vestibular nucleus neurons exhibit activity-dependent plasticity. The proposed research will use a brainstem slice preparation to examine the short and long term synaptic dynamics onto cerebellar target neurons, which mediate cerebellar influences on signaling and plasticity in the VOR. Distinct classes of cerebellar target neurons will be identified by their axonal projections and patterns of cerebellar synaptic cell terminals. The influence of vestibular nerve, commissural, and cerebellar synaptic activity will be examined in cerebellar target neurons and in other identified vestibular nucleus neurons. These studies will provide foundations for targeted investigations of the molecular mechanisms that underlie vestibulo-ocular reflex plasticity as well as for pharmacological treatments of cerebellar disorders and of oculomotor disorders that cause nystagmus. PUBLIC HEALTH RELEVANCE: The goal of this project is to identify cellular mechanisms of eye movement performance and plasticity, with a particular focus on cerebellar influence over the vestibulo-ocular reflex, which is critical for stabilizing images on the retina during self-motion. Cellular mechanistic analyses of vestibular and cerebellar control of eye movements are essential for developing therapeutic treatments both for cerebellar disorders including ataxias and neurodegenerative diseases as well as for devastating disorders of eye movements including nystagmus and consequent oscillopsia.